Carnitine-depleted cultures of human skin fibroblasts and of rat and human skeletal muscle cells were prepared. Their greatly depressed capacity to oxidize fatty acids was effectively restored on adding L-carnitine to the incubation medium. Carnitine concentration as low as 2.5 x 10 to the minus 8 M significantly stimulated the above process. Addition of carnitine to the depleted fibroblasts reduced incorporation of palmitate into glycerides. Consequently, carnitine seemed to counteract cellular accumulation of lipids. Dexamethasone increased palmitate oxidation independently of the effect of carnitine. Fatty acid oxidation in cultured fibroblasts from two patients with muscle carnitine deficiency responded normally to exogenous carnitine and dexamethasone. The results demonstrate a rationale for treating these patients with carnitine and glucocorticoids.